Clozapine-induced myocarditis: Two case reports and review of clinical presentation and recognition

Abstract

Myocarditis is a potentially fatal cardiac disease marked by inflammation of the heart muscle. With a noted black-box warning, rates of clozapine-induced myocarditis are reportedly as high as 3%. Since the first case of clozapine-induced myocarditis was documented in 1994, more than 250 cases have been described in literature with an approximate 33% case-fatality rate. We report 2 cases of patients with primary psychotic disorders treated with clozapine, who developed signs and symptoms of myocarditis. The first was a 35-year-old white male patient with a primary diagnosis of schizoaffective disorder (bipolar type) who was initiated on clozapine after nonresponse to several therapies. On day 26, the patient was admitted to the emergency department for chest pain presenting with eosinophilia and notable elevations in several biomarkers, including troponin and C-reactive protein. The second patient was a 45-year-old black male who was initiated on clozapine for treatment-resistant schizophrenia. On day 13, the patient reported cardiac-related concerns (tachycardia) and flu-like symptoms resulting in hospitalization. Similarly, this patient demonstrated elevated biomarkers (troponin and creatine kinase). Both patients experienced resolution of symptoms after discontinuation of clozapine. Clozapine was not rechallenged for either patient. Review of literature further elucidates the relationship between clozapine and myocarditis, including potential risk factors, pathophysiology, and symptom presentation. Due to the potentially fatal nature of this condition, clinical vigilance and awareness is warranted upon initiation of clozapine through monitoring of symptoms along with cardiac and inflammatory biomarkers as indicated.

Use of the new Lake Louise Criteria improves CMR detection of atypical forms of acute myocarditis

“…In other patients, myocarditis shows a cardiomyopathic presentation with acute or chronic heart failure, systolic impairment with or without left ventricle dilation or with new onset ventricular arrhythmias, high-degree atrio-ventricular block or bundle branch block [ 2 , 8 ]. Other confounding features are the variable clinical course (myocarditis can be acute, subacute, or chronic [ 9 ]), the underlying pathological substrate and the aetiology of the disease (viral or bacterial infections [ 10 ], toxins or drugs or autoimmune disorders [ 10 – 12 ]).…”

Non-ischemic Cardiomyopathy: A Rare Adverse Effect of Clozapine

“…Patients can present with nonspecific signs such as fever, fatigue, palpitations, acute chest pain, or overt signs of heart failure such as orthopnea, leg swelling, shortness of breath [6]. Clozapine-induced cardiomyopathy can occur as soon as three weeks after initiation of therapy till up to four years of continuous use of the drug but most cases occur within the first month of drug initiation.…”

Could N‐acetylcysteine improve the safety of clozapine?

“…Mechanisms behind these adverse effects are complex and not fully understood. They may involve immune-related mechanisms (Goldstein et al, 2014;Lacaze et al, 2020), direct toxic effects (Sackey, Moore, Cupples, & Gutierrez, 2018) and oxidative stress (Fehsel et al, 2005). Clozapine is bioactivated in a nitrenium ion by cytochromes P450 and myeloperoxidase system in leukocytes and their precursors.…”